Ex Parte Sigg et alDownload PDFPatent Trial and Appeal BoardJan 11, 201712722386 (P.T.A.B. Jan. 11, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 12/722,386 03/11/2010 Daniel C. Sigg P0034773.01(134.03410101) 3008 26813 7590 01/12/2017 MUETING, RAASCH & GEBHARDT, P.A. P.O. BOX 581336 MINNEAPOLIS, MN 55458-1336 EXAMINER OSINSKI, BRADLEY JAMES ART UNIT PAPER NUMBER 3763 MAIL DATE DELIVERY MODE 01/12/2017 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte DANIEL C. SIGG, DAVID SCHWARTZMAN, EDUARDO N. WARMAN, RODOLPHE KATRA, and SANJEEV G. SHROFF Appeal 2015-002136 Application 12/722,386 Technology Center 3700 Before ERIC B. GRIMES, ULRIKE W. JENKS, and ROBERT A. POLLOCK, Administrative Patent Judges. POLLOCK, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal1 under 35 U.S.C. § 134 from the Examiner’s rejection of claims 1—4, 6—10, and 21—37. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE According to the Specification, “[hjeart failure can be classified as heart failure with preserved ejection fraction (also referred to as diastolic 1 Appellants identify the Real Party in Interest as Medtronic, Inc. (App. Br. 3). Appeal 2015-002136 Application 12/722,386 heart failure) or as heart failure with reduced ejection fraction (also referred to as systolic heart failure).” Spec. 1:34—2:2. “Ejection fraction (EF) is the percentage of blood pumped out of the left ventricle with each heartbeat.” Id. at 1:29-30. The Specification discloses “methods of treating heart disease with the pericardial administration of an anti-fibrotic agent.” Id. at 2:14—15. “[T]he methods . . . may be used for the treatment of heart failure with preserved ejection fraction.” Id. at 6:28—29. Preferably, “the anti-fibrotic agent is relaxin . . . [which] is a naturally occurring peptide hormone.” Id. at 7:24-27. Claims 1 and 23 are representative of the claims on appeal and read as follows: 1. A method of treating a subject with heart failure with preserved ejection fraction, the method comprising: the determination that a subject suffers from heart failure with preserved ejection fraction, and the pericardial administration of an anti-fibrotic agent to the subject determined to suffer from heart failure with preserved ejection fraction. 23. A method of treating a subject with heart failure with preserved ejection fraction, the method comprising: the determination that a subject suffers from heart failure with preserved ejection fraction, and the delivery of relaxin into the pericardial space of the heart of the subject determined to suffer from heart failure with preserved ejection fraction. 2 Appeal 2015-002136 Application 12/722,386 The Examiner has rejected claims 1—4, 6—10, and 21—37 under 35 U.S.C. § 103(a) as obvious in view of Samuel2 and Struijker-Boudier3 (Ans. 2-4). The issues presented are: Does the evidence of record support the Examiner’s conclusion that the combination of Samuel and Struijker- Boudier would have made obvious a method of treating heart failure with preserved ejection fraction by the pericardial administration of an anti- fibrotic agent, as required by claim 1, or relaxin, as required by claim 23? We have reviewed Appellants’ contentions that the Examiner erred in rejecting claims 1—4, 6—10, and 21—37 as obvious over the cited art. App. Br. 6—18, Reply Br. 1—6. We disagree with Appellants’ contentions and adopt the findings concerning the scope and content of the prior art set forth in the Examiner’s Answer and Final Rejection.4 For emphasis, we highlight and address the following: Findings of Fact 1. Samuel discloses A method for treating cardiac fibrosis resulting from inj ury of a mammalian heart. . . [which comprises] the step of cont acting a therapeutically effecti ve amount of relaxin and/or an LGR7 activating agent with cardiac cells . . . in an amount sufficient to reduce the fibrosis. Samuel, Abstract. LGR7 “refers to a G protein-coupled receptor activated by relaxin H2.” Id. 144. 2 Chrishan Surendran Samuel et al., US 2006/0264367 Al, Nov. 23, 2006. 3 Harry A.J. Struijker-Boudier et al., US 2003/0009145 Al, Jan. 9, 2003. 4 Office Action mailed Dec. 12, 2013. 3 Appeal 2015-002136 Application 12/722,386 2. “Cardiac fibrosis is a hallmark of heart disease and ... is characterized by a disproportionate accumulation of fibrillar collagen.” Id. 12. “The proximal effector cells in this process are fibroblasts, which when activated to become myofibroblasts produce an excessive amount of collagen in response to inflammatory mediators.” Id. “Cardiac fibroblasts are the predominant source of synthesis of interstitial proteins and other myocardial components which have been implicated in heart failure by their effects on diastolic function and, indirectly, by effects on cardiac myocytes to cause or potentiate systolic dysfunction.” Id. 3. Samuel discloses that “[a]cute ischemic damage to the heart is associated with a progression to congestive heart failure.” Id. 13. “In addition to the original damage, the process of remodelling results in an even greater scarring response than necessary to mitigate the original damage . . . [which] leads to a compensatory response in the remaining tissue and an eventual hypertrophy and chronic failure.” Id. 4. Samuel discloses that “[cjhronic damage leading to cardiomyopathy is also associated with heart failure. Cardiomyopathy occurs when the heart becomes abnormally enlarged, thickened and/or stiffened due to fibrosis.” Id. 14. “This condition . . . may be caused by a wide range of conditions, including hypertension, chronic diseases, alcoholism, viral diseases, and others.” Id. “[T]he fibrosis associated with cardiomyopathies leads to a lessening in function of the tissue and decreased contractility.” Id. 5. Samuel discloses “methods for treating diseases related to cardiac fibrosis following either chronic or acute injury . . . [by] 4 Appeal 2015-002136 Application 12/722,386 administering ... a pharmaceutical formulation comprising . . . relaxin and/or an LGR7 activating agent to treat the resulting cardiac fibrosis.” Id. 110. “Reduction in fibrosis can be mediated by a decrease in fibroblast activation, myofibroblast differentiation, collagen synthesis, collagen deposition or matrix metal [ljoproteinase (MMP) expression. The effect of relaxin and/or an LGR7 activating agent on these processes may be direct or indirect.” Id. 6. Samuel discloses that relaxin ... is delivered to a patient via systemic delivery. ... In another embodiment, a therapeutically effective amount of relaxin ... is delivered to a patient via local delivery. Local delivery provides relaxin to the area of damage directly, and[] is a more targeted method for reduction of fibrosis in a specific area of injury. Examples of such delivery include . . . administration via the use of a stenting device, administration via a catheter . . . direct injection into or near the cardiac tissue, [and] injection into the pericardium. Id. 116. 7. Samuel further discloses an “association of fibrosis with the heart failure process in a variety of heart diseases, including those associated with both volume and pressure overload.” Id. f 54, “In the setting of heart failure, fibrosis involves an increase in both fibroblast number and matrix deposition . . . suggesting the importance of the fibroblast in the development of this condition.” Id. “Cardiac fibroblasts are also the predominant source of synthesis of interstitial proteins and other myocardial components which have been implicated in heart failure by their effects on diastolic function and, indirectly, by effects on cardiac myocytes to cause or potentiate systolic dysfunction.” Id. 5 Appeal 2015-002136 Application 12/722,386 8. Struijker-Boudier discloses compositions and methods that provide “sustained-release of a drug to the heart or coronary vasculature using an implanted dosage form that may be implanted in the cardiac or vascular tissue.” Struijker-Boudier, If 70. 9. Struijker-Boudier discloses compositions and methods that introduce “a cardiac drug into the pericardial space at a low volume and/or low dosage rate.” Id. 11 89. “The methods are particularly useful for drug delivery over an extended period of time for example, for delivery of drug at a low volume rate to reduce the risk, incidence, and/or severity of adverse side effects.” Id. “Introduction of the cardiac drug into the pericardial space can be via transpericardial or intrapericardial routes.” Id. 10. Struijker-Boudier discloses that an “advantage of the methods of the present invention is that relatively small quantities of a cardiac drug can be administered over an extended period of time to the pericardial space.” Id. “The methods . . . avoid the pitfalls associated with systemic delivery of a cardiac drug, namely that high systemic doses are often required to achieve an effective dose in the cardiac tissue . . . and such high systemic doses may have deleterious effects on non-cardiac tissues.” Id. Analysis As an initial matter, we accept the Examiner’s finding that “it is notoriously well known ... to diagnose a patient before treating them for a disease.” See Fin. Rej. at 4; Ans. 6 (citing Samuel, H 49, 53, 117). With respect to the cited art, the Examiner finds that Samuel discloses a method of treating heart failure comprising the pericardial administration of an anti- fibrotic agent such as relaxin. Ans. 2, citing Samuel, 116. The Examiner 6 Appeal 2015-002136 Application 12/722,386 finds that Samuel does not disclose “identifying and treating heart failure with preserved ejection faction specifically,” but “congestive heart failure [CHF] is divisible into two types preserved vs reduced ejection fraction or diastolic vs systolic heart failure and thus treating someone for CHF via the method of Samuel will treat preserved ejection fraction heart failure.” Ans. 2. With respect to pericardial drug delivery, the Examiner finds that Samuel “discloses using a local catheter” for heart failure treatment (Ans. 3, citing Samuel, 116), whereas Struijker-Boudier “discloses treating both types of CHF (systolic and diastolic . . .) via a local catheter . . . directly into the pericardial space” (Ans. 3, citing Struijker-Boudier, || 89, 96, and 217). The Examiner, thus, concludes that it would have been obvious to modify Samuel’s method by “identifying and delivering the medication directly into the pericardial space to treat either . . . type[] of CHF . . . [because] it is a known . . . delivery method for cardiac drugs to treat CHF.” Ans. 3. Appellants argue that claims 1 and 23 are directed “to methods of treating heart failure with preserved ejection fraction . . . [and] include at least two separate steps.” App. Br. 7. Appellants argue that, first, “a determination is made that a subject suffers from heart failure with preserved ejection fraction . . . [and] a second step involves the pericardial administration of an anti-fibrotic agent... or relaxin.” App. Br. 7. Appellants argue that “teachings of the generic treatment of chronic heart failure . . . [do not] teach or make obvious the selection of a specific subpopulation (those . . . with preserved ejection fraction)” for treatment. App. Br. 9. Appellants argue that “[h]eart failure with preserved ejection fraction and heart failure with reduced ejection fraction are separate and 7 Appeal 2015-002136 Application 12/722,386 unique diseases that require individual treatment.” App. Br. 9. Appellants argue that the combination of Samuel and Struijker-Boudier does not teach, “first, the selection of a specific population of subjects (those suffering from heart failure with preserved ejection fraction) and, second, the treatment of this selected group of patients.” App. Br. 10. Appellants’ arguments are not persuasive. The Specification discloses that heart failure can be classified as either heart failure with preserved ejection fraction (diastolic heart failure) or heart failure with reduced ejection fraction (systolic heart failure). See the Spec, at 1:34—2:2. Samuel discloses that relaxin and LGR7 can be used as anti-fibrotic agents to treat diseases related to cardiac fibrosis such as congestive heart failure. FFs 1 and 5. Samuel discloses that one mechanism of action of relaxin or LGR7 is an inhibition or decrease in fibroblast activation. FF 5. Samuel also discloses that, in the context of heart failure, fibrosis involves an increase in both fibroblast number and matrix deposition and that fibroblast activity is associated with both diastolic and systolic heart failure. FF 7. Struijker- Boudier teaches the benefits of pericardial drug administration of cardiac drugs. FFs 9—10. Finally, as noted by the Examiner, it is well known to diagnose a patient before treating them for a disease. See Ans. 6. In view of the above, we agree with the Examiner that the combination of Samuel with Struijker-Boudier would have made obvious methods of treating heart failure by determining that a subject suffers from heart failure with preserved ejection fraction, i.e. diastolic heart failure, and then administering an anti-fibrotic agent, as required by claim 1, or administering relaxin, as required by claim 23. 8 Appeal 2015-002136 Application 12/722,386 Appellants argue that one of skill in the art would not have a reasonable expectation of success in combining the teachings of Samuel and Struijker-Boudier to arrive at the claimed methods of treating a subject with heart failure with preserved ejection fraction. App. Br. 11. In particular, Appellants argue that Filippatos5 * * * 9discloses “the effectiveness of relaxin (‘serelaxin’) for the treatment of heart failure with preserved ejection fraction (‘HFpEF’), which ‘is rather unique as several classes that represent established therapies for HFrEF [heart failure with reduced ejection fraction] failed to provide similar benefits in HFpEF [heart failure with preserved ejection fraction]’.” App. Br. 12, citing Filippatos at 7—8. We do not find Appellants’ arguments persuasive. Appellants concede that Filippatos discloses that relaxin was effective for the treatment of heart failure with preserved ejection fraction. Even if other therapies that target heart failure with reduced ejection fraction are not effective at treating heart failure with preserved ejection fraction, Filippatos’ express disclosure that relaxin is effective rebuts previous results with other treatments. Appellants argue that “a person of skill in the art would have no common sense reason to modify the systemic delivery method of Samuel. . . [with] the pericardial administration [method]” taught by Struijker-Boudier. App. Br. 13. Appellants argue that Samuel discloses “that the preferred method of delivery is ‘via systemic delivery’ and presents a number of 5 G. Filippatos et al., Serelaxin in acute heart failure patients with preserved left ventricular ejection fraction: results from the RELAX-AHF trial, Eur. Heart J. 35(16): 1041—1050 (April 2014), submitted with the Information Disclosure Statement filed on February 12, 2014. App. Br. 12. 9 Appeal 2015-002136 Application 12/722,386 advantages for using systemic delivery.” App. Br. 13—14, citing Samuel, 116. Appellants argue that Samuel’s disclosure leaves the person of skill in the art with no reason to look for alternative delivery methods and the disclosure of Samuel would deter a person of skill in the art from attempting another type of delivery method, in particular a method which is more invasive and . . . [therefore] more expensive” and with more risk for the patient. App. Br. 14. Accordingly, Appellants argue, “a person of skill in the art would not be motivated to alter the teachings of Samuel for pericardial administration.” App. Br. 14. Appellants’ arguments are not persuasive. Samuel discloses that relaxin may be delivered to a patient via systemic or local delivery, and that local delivery is a more targeted delivery method. FF 6. Samuel also discloses that examples of local delivery include direct injection into or near the cardiac tissue and injection into the pericardium. Id. Struijker-Boudier discloses compositions and methods wherein cardiac drugs are introduced into the pericardial space. FF 9. Struijker-Boudier discloses that the methods are particularly useful for drug delivery over extended time periods at a low volume rate, which reduces the risk, incidence, or severity of side effects. FFs 9 and 10. In view of these disclosures, we agree with the Examiner that the “pericardial administration of an anti-fibrotic agent,” as required by claim 1, and that “the delivery of relaxin into the pericardial space of the heart,” as required by claim 23, would have been obvious to one of ordinary skill in the art for the purpose of avoiding side effects. 10 Appeal 2015-002136 Application 12/722,386 Thus, we affirm the rejection of independent claims 1 and 23 under 35 U.S.C. § 103(a).6 * * * * 11Dependent claims 2—4, 6—10, 21, 22, and 24—35 have not been argued separately and therefore fall with independent claims 1 and 23. See 37 C.F.R. § 41.37(c)(l)(iv). Appellants also argue the rejection of claims 36 and 37. Claims 36 and 37 depend from independent claims 1 and 23, respectively, and further require that “heart failure with preserved ejection fraction comprises an ejection fraction of about 50 percent or greater.” The Examiner finds that Samuel “does not disclose treatment if the preserved ejection fraction comprises an ejection fraction of about 50 percent or greater.” Ans. 4. The Examiner concludes, however, that it “would have been obvious to one of ordinary skill in the art... to determine over which ranges the treatment is effective, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art.” Ans. 4. Appellants argue that the Examiner’s reasoning is in error because “the combined teachings of Samuel and Struijker do not teach a method including a step of determining that a subject suffers from heart failure with preserved ejection fraction followed by the pericardial administration of an anti-fibrotic agent. . . or relaxin.” App. Br. 17. Appellants argue that, 6 Appellants also present arguments directed to the Examiner’s citation of the Toscano reference during prosecution (App. Br. 14—15). However, the Examiner did not cite the Toscano reference in the statement of the rejection and does not rely on Toscano’s disclosure in formulating the rejection. Therefore, we do not further consider these arguments. 11 Appeal 2015-002136 Application 12/722,386 therefore, “the general conditions of the claim have not been met and it cannot be routine experimentation [to] discover optimal or workable ranges.” App. Br. 17. Appellants’ arguments are not persuasive for the reasons discussed above. Thus, we affirm the rejection of claims 36 and 37 as being obvious in view of Samuel and Struijker-Boudier. Conclusion of Law The evidence of record supports the Examiner’s conclusion that the combination of Samuel and Struijker-Boudier would have made obvious a method of treating a subject with heart failure with preserved ejection fraction by the pericardial administration of an anti-fibrotic agent, as required by claim 1, or relaxin, as required by claim 23. SUMMARY We affirm the rejection of claims 1—4, 6—10, and 21—37 under 35U.S.C. § 103(a). TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 12 Copy with citationCopy as parenthetical citation